IOV > IOV > Management > Direzione Scientifica
- Prof. Giuseppe Opocher (supplente)
La Direzione Scientifica promuove e coordina la ricerca clinica e sperimentale dell’Istituto.
In aderenza al mandato della Giunta Regionale del Veneto e del Ministero della Salute, promuove lo sviluppo delle collaborazioni scientifiche a livello di tutta la regione e integra le attività di ricerca clinica e sperimentale condotte nelle diverse realtà provinciali in un programma unitario condiviso.
Dopo il riconoscimento del carattere di I.R.C.C.S. da parte del Ministero della Salute nel 2005, nel triennio 2005-2007 si è provveduto a costituire il primo nucleo della rete scientifica utilizzando i finanziamenti della Regione per la Ricerca Finalizzata, i finanziamenti del Ministero della Salute per la Ricerca Corrente e Finalizzata ed i finanziamenti elargiti da Enti Pubblici e Privati.
Linee di Ricerca
Tumor Epidemiology and Prevention
Akin most (if not all) fields of medicine, progress in oncology firmly relies on the growing body of evidence about the mechanisms underlying neoplastic transformation and tumor progression. On the other hand, this wealth of knowledge cannot prescind from the careful consideration of the possible causes that promote cancer generation, including environmental factors, nor can the incidence of the different cancer forms be ignored, since its fluctuations over the years may reflect significant variations in the impact of these factors on the general population.
Thus, in-depth knowledge of the prevalence and incidence of different cancer forms may greatly help in designing primary prevention strategies addressing exogenous factors or habits causally related to tumor generation. Secondary prevention as well may strongly impact on cancer morbidity and mortality, and the importance of appropriate screening strategies for early diagnosis of some tumors is largely proven.
At the IOV, particular attention is paid to primary and secondary prevention of tumors, and the Institute has the mission of coordinating the three major cancer screening programs over the entire Veneto region, in strict collaboration with local health authorities.
Mechanisms of Cancerogenesis
Neoplastic transformation is a complex process that involves several initiating and/or promoting events, numerous as yet imperfectly understood molecular changes in
the cell, and bidirectional interactions mediated by soluble or cell-associated molecules between tumor cells and the microenvironment (endothelial cells, stromal cells, infiltrating inflammatory cells). Among the causes underlying neoplastic transformation, infectious agents may play a relevant role, and it is estimated that >20% of human neoplasias are associated with viral infections.
The immunocompromised status, due either to infection or iatrogenic immunosuppression in transplant recipients, also favors the development of virus-associated tumors. At the IOV, a great deal of expertise has accumulated over the past 40 years on the pathogenic role of viruses, in particular the human T lymphotropic virus type 1 (HTLV-1), the Epstein-Barr virus (EBV), the human herpesvirus type 8 (HHV8 or Kaposi Sarcoma-associated HerpesVirus, KSHV), the human papilloma virus (HPV).
These viruses play a direct role in oncogenesis and behave as causative agents of several tumors; instead, non-transforming retroviruses, such as the human immunodeficiency virus (HIV), are involved in the oncogenetic process through indirect mechanisms, by favoring reactivation of transforming viruses and/or interfering with the physiologic pathways that regulate cell proliferation and death. Analysis of the mechanisms by which viruses rearrange the cellular program of senescence/immortalization would shed new light into cell physiopathology and provide new tools for prevention/treatment strategies.
Instrumental and Molecular Approaches for Diagnosis, Staging and Follow-Up
A large body of evidence on accumulating genetic changes that underlie tumor development is providing more and more powerful tools for the clinical evaluation of
the neoplastic disease. The characterization of new molecular features is significantly contributing to redefine both the criteria of tumor diagnosis and the formulation of prognosis. Indeed, if we only consider mammary tumors, what 20 or 30 years ago we called a “breast cancer” is now known to be an array of different transformation processes, each endowed with special phenotypic and genotypic properties, that differentiate this tumor from tumors apparently similar by conventional histology.
As a matter of fact, a molecular classification of cancer is flanking the classical tumor taxonomy, and patients are increasingly classified based on the molecular profile of their tumor. Thus, the definition of new, non-invasive markers for tumor diagnosis, staging and prognosis is urgently needed. While the identification of new molecular markers (in tumor cells or in biological fluids) is clearly fundamental to the goal of improving the definition of prognosis of neoplastic diseases and to help in predicting the response of individual patients to targeted therapies, progress in tumor diagnosis and monitoring also firmly relies on the availability of new technological developments in several different fields.
In this frame, the Institute has privileged the development of various instrument-based platforms, particularly those best suited to neoplastic conditions of major interest to the Institute.
Innovative Therapeutic Approaches: Chemotherapy, Radiotherapy and Surgery
The wealth of knowledge accumulated on the molecular alterations that characterize tumors has profoundly changed pharmacological approaches to tumor therapy, with surgery, radiotherapy and chemotherapy now flanked by the so-called “target therapies”, which rely on the ability of small molecules to more or less specifically and selectively interfere with abnormal intracellular pathways responsible for the growth advantage of transformed tumor cells.
Thus, several national and international clinical protocols are active at the Institute, with special attention placed on the possibility of combining small molecules such as kinase inhibitors with biologically active tools such as monoclonal antibodies. In any case, all cancer patients are offered an integrated approach to diagnosis and treatment that involves the expertise of medical oncologists, surgeons, radiotherapists, psycho-oncologists, and if needed specialists from many other fields, interacting in a multidisciplinary unit.
Of course, the search for new, more active, selective and tolerated therapies cannot proceed in the absence of continuous exchange with the laboratory, and laboratory expertise is essential to this integrated approach.
Many so-called “intelligent” drugs are now available, in fact; nothing, however, could be worse than using intelligent drugs in a stupid manner, that is, administering a drug to patients who cannot benefit from it due to their constitutional features or the molecular properties of their tumor.
Tumor Immunology and Innovative Therapeutic Approaches
It is now widely accepted that tumor growth is the result of the very complicated bidirectional interaction between cells that progressively acquire molecular alterations, a growth advantage and finally a fully transformed phenotype, and surrounding cells of the host that may contrast or in some instances also favor their autonomous growth and expansion. In addition, the interplay between tumor cells and host tissues may change during the course of tumor development.
In a first phase a “sneaking through” situation may occur, where immune surveillance simply disregards cells on the way to premalignant or malignant transformation. Later on, an equilibrium may arise between tumor cell growth and death by apoptosis on the one hand, and active control by immune effectors on the other, with tumor expansion still in check. The final overt tumor expansion phase arises when this unstable equilibrium somehow breaks down, during which tumorderived factors often come into play to abate the residual contrasting potential of immune surveillance.
For many years, one of the most popular dreams of tumor immunologists has been the so-called “magic bullet”; while this goal is close to becoming realized thanks to monoclonal antibodies and target molecules, the other great dream of potentiating the immune response against tumors has not lived up to its promise. Notwithstanding, tumor immunology is currently undergoing a new flare of development, thanks to the understanding that a combination of different strategies synergizing against all (or most) the different actors contributing to tumor growth could be a very effective, if not the ultimate, remedy.
While several of these approaches are already in phase I/II clinical trials, frequently in combination with canonical chemotherapeutic tools, many others are still in a preclinical, translational research phase; hopefully, some of them will soon move to the human setting and become a part of the therapeutic armamentarium of clinical oncologists.
Quality of Life in Cancer Patients and Geriatric Oncology
Besides the effort spent in translational and clinical research, much attention is paid at the Institute to the issue of quality of life in cancer patients, with a special focus on geriatric oncology. Persons over the age of 65 years are the fastest growing segment of the population and will account for an estimated 20% of Americans and 25% of Europeans by the year 2030. Cancer incidence is 11-fold higher in persons over the age of 65 years than in younger ones. Treatment of elderly patients with cancer is one of the key areas in which clinical and scientific activities of our Institute are focused.
Close relationship with the Geriatric Clinics of the University of Padova is a peculiar feature of our Geriatric Oncology Program; a multidisciplinary team including oncologists, psychologists, geriatricians, cardiologists, dieticians, endocrinologists and other health professionals is currently involved in the evaluation and care of elderly patients. Multidimensional geriatric assessment (MGA) is regarded as an indispensable tool in the management of cancer patients. The Performance Status (PS) is one of the most useful instruments orienting the therapeutic decision in adult patients, but it is considered as a rather blunt tool when dealing with the elderly, for which MGA is much more appropriate, as it covers the multifaceted features of ageassociated conditions.
Monthly case-oriented multidisciplinary meetings are organized in order to share clinical problems and to develop common algorithms of treatment according to tumor site, stage and MGA parameters. In this occasion a review of pertinent literature and results of our trials are presented to complete the discussion of clinical cases. A database containing demographic, clinical and follow-up data of more than 600 patients evaluated by MGA has been created and has provided data for several communications to international congresses and scientific articles.
Particular attention has been devoted to proposing clinical trials to elderly patients whenever a national or international protocol is open at our Institution, because we believe that elderly patients must be enrolled in clinical trials, even though much more time and effort is needed.
Ultimo aggiornamento: 09/01/2013
|Direttore||Prof. Giuseppe Opocher (supplente)|
|Personale Amministrativo - Responsabile Amministrazione della Ricerca||Sig.ra Daniela Battistuzzi|